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Improvement of Sleeping Beauty Transposon System Enabling Efficient and Stable Protein Production

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Abstract

The most essential goal in the field of biopharmaceuticals is to develop cell lines with higher protein yields. To this goal, the Sleeping Beauty (SB) transposon-based expression system has been developed as a powerful tool for increasing protein productivity. However, SB transposon system has fallen short of expectation in terms of the efficiency and stability of protein production, limiting its applicability to large-scale production of recombinant proteins. Here, we propose a novel strategy to increase the efficiency and stability of protein production, through modification of the traditional SB transposon vector. Adding a pair of inverted terminal repeats (ITRs) next to existing ITRs (i.e., double-ITRs) significantly increased the efficiency of transgene integration, resulting in high-yield and sustained protein production. Furthermore, double-ITRs responded more favorably to DNA methylation inhibitors in terms of protein yield, implying that using double-ITRs with DNA methylation inhibitors may be effective in increasing protein productivity. Taken together, our study introduces a new vector platform that is applicable to high-yield and sustained protein production, and will open new avenues in the field of biopharmaceuticals.

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Acknowledgements

This research was supported by an Incheon National University research grant (2020-0070).

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Authors and Affiliations

  1. Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Korea

    Yun Haeng Lee, Ji Yun Park, Eun Seon Song, Haneur Lee, Myeong Uk Kuk, Junghyun Joo & Joon Tae Park

  2. Convergence Research Center for Insect Vectors, Incheon National University, Incheon, 22012, Korea

    Joon Tae Park

  3. Department of Chemical and Environmental Technology, Inha Technical College, Incheon, 22212, Korea

    Hyungmin Roh

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  1. Yun Haeng Lee
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Contributions

YHL, HR, and JTP conceived of and designed the experiments. YHL, JYP, ESS, MUK, JJ, and HL performed the experiments. YHL analyzed the data. YHL, HR, and JTP wrote and edited the manuscript.

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Correspondence to Hyungmin Roh or Joon Tae Park.

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Lee, Y.H., Park, J.Y., Song, E.S. et al. Improvement of Sleeping Beauty Transposon System Enabling Efficient and Stable Protein Production. Biotechnol Bioproc E 27, 353–360 (2022). https://doi.org/10.1007/s12257-021-0231-x

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